Study of genetic diseases with neoplastic manifestations and detailed investigation of families at high risk of cancer may help detect environmental and genetic influences in carcinogenesis, especially when appropriate laboratory assays are used. Methods include review and documentation of prior medical and environmental history; collection and distribution of biological specimens; and review of hospital records of patients with selected genetic diseases or neoplasms. Reports were made on 7 cancer families, a series of patients with multiple neurofibromatosis and rhabdomyosarcoma, and 3 individually informative patients, including a girl with acute lymphoblastic leukemia and neurofibromatosis, and a man with osteosarcoma and a new malformation syndrome, resembling but distinct from Waardenburg syndrome. The hereditability of SV40 T antigen expression and the baseline frequency of sister-chromatid exchange in 5 cancer families were also reported. The same approach will be continued, using new laboratory methods and epidemiologic clues from other sources as available.